Gastroesophageal reflux is a series of clinical syndromes caused by frequent reflux of gastric contents into the esophagus through the lower esophageal sphincter. I. Mechanism of gastroesophageal reflux causing asthma 1. Vagus-mediated reflex: The tracheobronchial tree has the same embryonic origin as the esophagus, with the distal esophagus developing from the embryonic lung buds, that is, from the respiratory system, and both are autonomously innervated by the vagus nerve. In human studies, intraesophageal acid has been found to increase total respiratory resistance by 10%, especially during the onset of reflux symptoms, up to 72%, and in experiments using dogs as a model, it was found that this increase in respiratory resistance caused by intraesophageal acid could be eliminated by bilateral vagal nerve dissection. Wright et al. evaluated 136 patients and found that intraesophageal acid significantly reduced 1 S forceful expiratory flow (FEV ) and oxygen saturation, and that this change disappeared when pretreated with atropine.Field et al. analyzed data from 312 asthmatic breathers and found that when symptoms of GERD were present, FEV. peak expiratory flow (PEF) and airway resistance changed by 3% , 35% , and 42% , respectively. These changes can usually be partially blocked by atropine and vagotomy. It is evident that vagally mediated reflexes play a major role in the process of GERD leading to asthma. Recent findings also suggest that asthma patients with GERD are often accompanied by autoregulatory impairment of vagal hyperresponsiveness, which leads to a decrease in lower esophageal sphincter pressure and frequent transient lower esophageal sphincter relaxation, the main mechanism by which reflux occurs. 2, bronchial hyperresponsiveness: Intraesophageal acid can enhance bronchial hyperresponsiveness to other stimuli such as acetylcholine. wu et al. l6] perfused 7 voluntarily tested asthmatic patients with 0.1% hydrochloric acid and saline intraesophageally, and then evaluated the airway responsiveness with acetylcholine-induced changes in respiratory function due to asthma. it was found that the hydrochloric acid perfusion group decreased FEV. by 35% of acetylcholine concentration was significantly lower than that of the saline perfusion group. In contrast, Bagnato et al. performed acetylcholine provocation test on 30 patients with GERD without asthma symptoms and 30 normal subjects at the same time, and used the acetylcholine concentration that caused a 20% decrease in FEV. as an index to evaluate airway responsiveness, and found that 11 of the 30 patients were equal to or less than this index, while only 2 of the control group were equal to or less than this index. Vincent et al. also demonstrated that in the number of esophageal refluxes and bronchial reactivity. There is an association between Although there is no data showing that anti-reflux treatment can improve airway hyperresponsiveness, these data do suggest that airway hyperresponsiveness due to esophageal reflux plays an important role in the development of asthma. 3. Microinhalation: Animal experiments have confirmed that the increase in airway resistance due to tracheal acidification is several times higher compared to esophageal acidification. Tuchman et al. observed in adult cats that 10 ml of acid in the esophagus can cause a 1.5-fold increase in total lung resistance, whereas 0.5 ml of acid in the trachea can cause a 5-fold increase in total lung resistance. Similarly, monitoring both tracheal and esophageal pH in patients with asthma, Jack et al. demonstrated that intraesophageal acid caused an 8% decrease in PEF , and an 84% decrease in PEF when intraesophageal acid caused a decrease in intratracheal pH . The above study shows that if trace inhalation is present, it will significantly increase airway reactivity. 4, airway inflammation: Some studies have confirmed that in a guinea pig model, intraesophageal acid can activate the local axonal reflex, i.e., intraesophageal acid causes the release of inflammatory substances such as substance P in the bronchial mucosa through local nerve reflexes, resulting in airway edema. Inhaled citric acid was also found to cause a dose-dependent increase in pulmonary resistance, accompanied by sensory nerve activation and peripheral neurokinin release, and the increased total pulmonary resistance was eliminated by kinin NK-2 receptor antagonists.l8 J. This suggests that the airway inflammatory response also plays an important role in the mechanism of asthma caused by GERD, which provides a rationale for the use of kinin and bradykinin antagonists in the treatment of asthma with GERD. This provides a rationale for the use of kinin and bradykinin antagonists in the treatment of asthma with GERD. 5. Ventilation changes: Although there are many experiments in which intraesophageal acid causes bronchospasm, there are also reports of intraesophageal acid causing neither changes in FEV. nor bronchospasm. Field et al L5 J reviewed 18 sets of trials of airway responses to intraesophageal acid in 312 patients with asthma from 1966 to 1997 and found that changes in PEF occurred in 35% of patients, changes in airway resistance in 42%, and no changes in FEV. in 90%, and they concluded that bronchospasm does not play a major role in the development of asthma and is not present in all patients with asthma. These findings led Field et al. to try to find other possible causes to explain asthma symptoms associated with GERD, and it turned out that intraesophageal acid could cause significant changes in microventilation and respiratory rate, so they inferred that this could be another explanation for GERD-related asthma symptoms. II. Mechanisms of asthma causing GERD Airway obstruction during the onset of asthma increases the negative pressure in the thoracic cavity, which increases the pressure gradient in the diaphragm and predisposes to esophageal reflux. In addition, airway obstruction flattens the diaphragm, weakening its anti-reflux capacity. The application of theophylline drugs in the treatment of asthmatic patients can increase gastric acid secretion and decrease lower esophageal sphincter pressure, inducing reflux or worsening reflux symptoms in patients. In an open-label trial, Eksiroh et al. found a 24% increase in reflux duration and a 3-fold increase in reflux symptoms after theophylline treatment. Similarly, systemic application of a monoadrenergic agonist reduced lower esophageal sphincter pressure but showed no such effect in non-asthmatic patients Ruzkowski et al. found in a small crossover trial that inhalation of a monoadrenergic agonist reduced the incidence of GERD symptoms in patients by 40% compared to the application of theophylline. III, manifestations of esophagitis, their acid reflux was 3 to 5 times higher than those with improvement, suggesting that it is important to prolong the duration of acid suppression therapy before determining the outcome. Studies by several other authors have reached similar conclusions, such as Harding et al_l mari treated 30 patients with asthma with GERD with increasing doses of proton pump inhibitors, and a pre- and post-treatment outcome assessment found that at least 73% of patients had improved PEF and/or reduced asthma symptoms. Asthma symptoms improved over time, with 30% of patients showing improvement at 1 month, 43% at 2 months, and up to 57% at 3 months. Among those with improvement, FEVl, FEVl/FVC and PEF improved significantly in 25-75% of cases. F0rd et al. treated 11 patients with nocturnal asthma with GERD with omeprazole 20 mg daily for 4 weeks and found no change in asthma symptoms or PEF compared to the placebo group. In a randomized, placebo-controlled, crossover trial, Teichtahl et al. also treated 20 patients with nocturnal asthma with GERD with omeprazole 40 mg daily for 4 weeks and found no significant changes in asthma symptoms, inhaled monoadrenergic agonist dose, morning PEF, or respiratory function. Furthermore, these patients underwent intraesophageal acid testing and found no reduction in the duration of acid exposure. 2. Surgical treatment: Field et_l conducted a retrospective study of 24 trials of surgical treatment of acid reflux from 1966 to 1998, including 417 patients with asthma, and found that after surgical treatment with antacid, 90% of patients had improved GERD symptoms, 79% had improved asthma symptoms, 88% had reduced dosage of anti-asthma medication, and 27% had pulmonary function The trial’s design was flawed. Despite the design flaws of some trials, there is evidence that at least 70% of patients with asthma symptoms improved significantly after anti-reflux surgery. 3. Comparison of surgical versus pharmacological treatment: Larrain et al. compared the effects of cimetidine 300 nag four times daily with surgical treatment and found improvements in FEV, PEF and drug use in both the pharmacological and surgical groups compared with the placebo group after 6 months of treatment. Asthma symptoms improved by 36% in the control group, 74% in the medication group, and 77% in the surgical group. In contrast, Sontag et al. compared the effect of treatment with ranitidine 150 mg three times a day and surgery in 72 asthmatic patients with gastroesophageal reflux, and found that at 5 years follow-up, asthma symptoms were reduced or improved in 75% of patients in the surgical group, compared to 9% and 4% in the ranitidine treated and control groups. Thus, Menes et al_l J concluded that anti-reflux surgical treatment was superior to H, receptor blockers, but there is insufficient information to compare the difference between surgical treatment and proton pump inhibitor treatment for the control of asthma symptoms.